This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We will prepare macromolecular complexes of HIV-1 reversetranscriptase (RT), an essential component in the life cycle of theHIV-1 virus, with nucleic acid and nucleoside and nonnucleoside reversetranscriptase inhibitors. The three dimensional structures of thesecomplexes will be determined by x-ray crystallographic methods. Throughthese studies we hope to gain a detailed understanding of thefundamental principles underlying inhibition of RT's function and theemergence of resistance to these inhibitors. Ultimately we hope toapply information garnered from our stuctural studies towards theadvancement of new and effective treatment stategies in the form ofbetter anti-HIV drugs.